1. Treatment of children with rare metabolic diseases in Poland benefits of centralized system Jolanta Sykut-Cegielska, MD, PhD, Ass Prof Department of Metabolic Diseases, Children’s Memorial Health Institute

2. Rare diseases are a real health care issue In the EU the no of people with rare diseases is ≈35 million There are 6000-8000 different rare disorders (www.orpha.net)www.orpha.net 80% of rare diseases are genetic 50% of the patients die in the childhood Rare (orphan) disease = less than 5 in 10,000 people

3. Represent some of the rarest, but most life-threatening unmet medical needs Disease with a specific enzyme deficiency arising from single or multiple gene defects, leading to a block in a metabolic pathway and overt clinical signs and symptoms

4. IEMs classification Disorders of metabolic intoxication (intermediate metabolism, leading to progressive accumulation of toxic products proximal to the metabolic block) Disorders of energy metabolism Disorders of complex molecules (synthesis, breakdown or transport)

5. „… in inborn errors of metabolism treatment should be implied rather as removal or even prevention of the effects of genetic defect through mitigation or elimination of clinical symptoms…” Physician’s guide to the treatment and follow-up of metabolic diseases Nenad Blau, Georg Hoffmann, James Leonard, Joe Clark, eds. 2006, Springer

6. IEMs classification & treatment Disorders of metabolic intoxication Disorders of energy metabolism Disorders of complex molecules Detoxification by extracorporal exchange and drugs, special diets and products (FSMP)… Symptomatic / supportive Enzyme replacement therapy, substrate reduction therapy, BMT, HSCT… Advanced therapies based on genes and cells, tissue engineering …

7. IEMsorphan drug orphan drug research → development → access Translation research into development orphan designation → marketing approval basic research → clinical research → clinical practice

8. In 2000 y. the EU Regulation on Orphan Medicinal Products came into force, stimulating the development of orphan drugs Distribution of orphan designation by therapeutic class [COMP report]

9. Proportion of marketing approval by FDA for IEM drugs was significantly higher than that for non-IEM orphan products. The most designations and approvals for LSD (43 and 9, respectively during 25 yrs) [Sonali et al Pediatrics 2011]

10. Therapeutical health program 2008200920102011 (JAN-JUL) Patients no Payments (in Euros) Patients no Payments (in Euros) Patients no Payments (in Euros) Patients no Payments (in Euros) Gaucher disease therapy 564 409 037616 239 51664 6 099 344577 015 312 MPS type I therapy16 988 931191 951 78718 2 937 634171 857 436 MPS type II therapy0 - 181 752 5753710 067 634357 305 156 MPS type VI therapy0 - 3 659 8024 6 806 6123 981 413 Pompe disease therapy 0 - 19 1 515 70818 3 160 170191 952 114 Total725 397 96812012 119 38814129 071 39413119 111 431 Source: NFZ BO6,5 (07.09.2011) Public resources for treatment of IEMs in Poland

11. Qualification to at least the most expensive therapies, is now based on clear rules (created by MoH and NHF). Since 2009 y. Coordinating Team (called up by NHF) has been responsible for either qualification or verification of treatmentin IEMs.

12. Coordinating Team for Ultrarare Diseases 15 meetings since 08June2009 to 20June2011 503 applications were considered 442 - qualified for financing 18 - excluded from therapy 11 - not fulfiled inclusion criteria 19 - applications to be completed 10 - charity therapy 3 - no patient’s consent

13. LSD are an IEM success story (with regard to development of new therapies), but such success elswhere is needed, e.g. a notable absence of marketing approval for any designated products for mitochondrial diseases (in USA 7 designations and 0 approvals). [FDA data, 2011]

14. FSMP and orphan drugs access in Poland Availability ≠ access No temporary approval By compassionate use procedures Off-label use as a decision of regulations of „treatment experiment”, after unsuccesful application of standard treatment methods

15. Benefits of centralized system Dept Metabolic Diseases in CMHI – reference center for IEMs for Poland (by reputation) Network of Polish metabolic centers Selective screening program for IEMs – early detection of metabolic patients Polish Metabolic Group in the Polish Paediatric Society since 2001 4th Eastern European Metabolic Academy 2011 Educational courses for affected families (cooperation with patient associations) Participation in multinational clinical trials Partnership in international networks

16. General objective To promote health for children, adolescents and adults with rare organic acidurias (OADs) and urea cycle defects (UCDs) in Europe. Specific objectives 1. European patient registry: to describe the natural history, epidemiology, current diagnostic and therapeutic strategies, to provide information to national and EU healthcare authorities  improving knowledge; evaluating current strategies 2. European evidence-based consensus care protocols provided via a website in official EU languages  providing structured information for patients, parents and healthcare professionals, improving care, providing a template for national diagnostic and therapeutic guidelines and patient brochures

17. Birmingham London Rotterdam Warsaw Porto Barcelona Padua Zagreb Copenhage n Manchester Amsterdam (AMC) Düsseldorf Milupa SHS Prague Munich (LMU) Lisbon Zürich Istanbul Rome Bruxelles Lille WP leader Innsbruck Heidelberg Thessalonik i Paris Bern Madrid Valencia 75% coverage of the EU population

18. Currently: 3 continents 19 countries 46 partners 13 associate 33 collaborating OEA as a partner specific training courses: e-learning on NH3 9th European Metabolic Course (Warsaw, 25-29.09.2012)

19. How to improve IEMs treatment in Poland? Harmonization and coordination of all activities Through establishing national reference centres and centres of expertise for IEMs with mission of integrated and coordinated professional care, research and education/training Specific framework of health care for metabolic patients national plan for rare diseases (according to EU Council Recommendation 5June2009)

20. Thank you for your attention! RDD 2011, Warsaw